Five embryonic fields regulate tumor and/or colony formation of their closely related neoplasms: the mechanism of regulation of embryonal carcinoma by the blastocyst, which results in chimeras, appears to be by-inducing differentiation of malignant stem cell lineages to.normal cell lineages responsive to developmental and homeostatic control. The mechanism is specific for embryonal carcinoma cells, because other tumor cell types are not regulated, and it depends upon a soluble activity in blastocele fluid in the presence of contact with blastocyst cells. Logistical problems in acquiring enough blastocysts to make analysis possible have been overcome by the use of a line of embryonal carcinoma that differentiates into blastocysts indistinguishable from normal blastocysts. The fluid from normal and neoplastic blastocysts each inhibit the growth of embryonal carcinoma cells in vitro and contain similar electrophoretic bands. These neoplastic blastocysts can be mass produced and will serve as the initial material for this proposal, making it necessary to do only confirmatory work on the normal blastocysts. In addition, based upon Braun's demonstration of the secretion of growth factors in plant teratomas and in the embryonic plant, and the secretion of PDGF by embryonal carcinoma and its presence in the blastocyst, 7 embryonal carcinomas apparently each representing a stage in the development of the peri-implantation mouse embryo will be used to produce neoplastic ascites or conditioned media for identification of growth and differentiating activities such as those in blastocysts which regulate normal inner cell mass and embryonal carcinoma cells by autocrine and paracrine modes.